The neurotropic properties of human immunodeficiency virus (HIV) are well established, as is the ability of HIV to cause primary neurological and psychological abnormalities in persons with overt acquired immunodeficiency syndrome (AIDS). There is little information, however, on the prevalence, clinical manifestations, natural course, and potential public health impact of neuropsychological aberrations in less severe forms of HIV infection. We will address these issues by conducting case control and prospective cohort studies in three groups of homosexually active men: 80 with persistent generalized lymphadenopathy (CDC group III HIV infection), many of whom have been studied in detail by us for up to four years; 80 asymptomatic HIV- seropositive men (CDC group II); and 80 HIV-seronegative men. Each subject will undergo serial detailed neurologic examinations, standardized neuropsychological (psychometric) testing, culture of peripheral blood lymphocytes for HIV, and monitoring of T lymphocyte subsets. The neuropsychological tests will include measurements of intelligence, attention, concentration, long- and short-term memory, cognitive flexibility, information processing, motor speed, visual discrimination, and other characteristics. Sixty of the HIV-infected subjects (30 each with group II and group III HIV infection) will undergo annual lumbar punctures with cerebrospinal fluid culture for HIV and determination of intrathical production of antibody to HIV. A subset of 40 subjects with stage II and 40 with stage III HIV infection (all of whom will undergo the CSF studies) will have serial magnetic resonance brain scans. The natural history of the neuropsychological manifestations of HIV infection will be determined by longitudinal followup for up to five years.